ASA: Radiation lowers local recurrence risk for DCIS patients with close or positive margins

SAN DIEGO – Radiation may benefit women with ductal carcinoma in situ (DCIS) who have breast-conserving surgery if their tumor margins are close or positive; however, wide tumor margins alone also may convey the same protection from local recurrence, Dr. Kimberly Van Zee reported at the annual meeting of the American Surgical Association.

Dr. Van Zee and her colleagues on the breast surgery service at New York’s Sloan Kettering Cancer Center examined the data from a large institutional database of DCIS patients to assess the relative benefit of radiation for various margin widths. They discovered that after adjusting for the other variables, patients with the widest tumor margins saw very little reduction in risk of 10-year recurrence when radiation was added – only 6%. However, this was still a significant difference and represented a hazard ratio of 0.54. Radiation gave patients with positive margins an absolute 18% risk reduction, for a hazard ratio of 0.10.

“We know that radiation reduces risk in all subsets of women with DCIS undergoing breast-conserving surgery,” she said. “But we really wanted to evaluate the relationship between margin width and recurrence and find the best margin width for DCIS with breast-conserving surgery.”

Dr. Kimberly Van Zee

Over 20% of breast cancers are DCIS, and though overall mortality is low, as many as one in three patients will have local recurrence of their cancer. Radiation reduces the risk of local recurrence by about 50%, but it does not reduce the already low mortality associated with DCIS, she said.

Since radiation for DCIS may be associated with an increased risk for cardiovascular disease and certain rare malignancies, Dr. Van Zee said she and her colleagues were interested in identifying those women who were already at low risk for recurrence and would see little increased benefit from radiation.

Dr. Van Zee and her associates conducted a retrospective review of a prospectively collected database of women with DCIS who received treatment at Sloan Kettering Cancer Center between 1978 and 2010. The database contained multiple patient- and procedure-specific variables that were also factored into multivariable analysis in order to evaluate the relationships between margin width and recurrence, and to account for the contribution of radiation to reducing the risk of recurrence in women who received breast-conserving surgery for DCIS.

Overall, the database contained data for nearly 3,000 patients. Of the 2,996 studied, 72% were over the age of 50 and about 67% were postmenopausal. In 87% of cases, the diagnosis was made radiologically rather than clinically, and 60% of the patients had low or intermediate nuclear grade disease.

Dr. Van Zee and her colleagues assessed the 10-year recurrence rate for the 2,788 women whose excision margin width was known. Only 3% of these women had positive margins, and 75% had margin widths greater than 2 mm.

On multivariable analysis, wider margin width was associated with a significantly decreased 10-year risk of recurrence, but only for individuals who had not received radiation (P less than .0001). The hazard ratios for recurrence became progressively lower as margins widened, dropping to 0.31 for a margin of 10 mm or more.

Dr. Van Zee noted that the study was limited by its retrospective nature and the relatively small number of cases with positive margins. Also, cases with positive or close margins usually had more limited or focal disease at the margins, so recurrence rate estimates for this group may have underestimated risk of recurrence for those who had more significant disease.

During the discussion following her presentation, Dr. Van Zee noted that multiple factors are related to the risk of local recurrence, and that nomograms exist to help calculate risk and guide the decision to recommend radiation in women with close margins.

Dr. Patrick Borgen, chairman of the department of surgery at Maimonides Medical Center, New York, remarked that “biology beats technique. A growing wealth of information exists that there is a reservoir of DCIS that will progress so slowly as not to be significant. Is the next step in refining our approach better class prediction using genomic profiling?”

Dr. Van Zee agreed that genomic profiling will play a role, but noted that a study comparing DCIS score and multiple clinical variables would be expensive and archival pathology specimens would be difficult to obtain. Studies will mostly have to be prospective, she said.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.